This project will develop a new imaging technique which improves the localization and the accuracy and precision of in vivo measurements of single-photon radiopharmaceutical. The project will incorporate a medical imaging system (X-SPELT) which uses adjacent conventional CT and SPELT imaging systems for correlating emission-based functional data and anatomical data from a coregistered x-ray transmission image. This proposal encompasses 4 specific aims. (1) We will develop techniques to compensate the radionuclide data for the effects of the geometric response of the SPELT system including (a) quantifying the radionuclide data with regions of interest defined on the CT image, and (b) defining recovery coefficients with structural information from the CT image to compensate the SPELT image for partial volume errors, and (c) incorporating structural information directly with the SPELT reconstruction algorithm. (2) We will develop scatter distribution using a technique which incorporates structural information from the CT-derived attenuation map, and compare it against conventional scatter correctin techniques. (3) Phantom experiments of tumor and myocardial perfusion imaging will be performed to evaluate the compensation techniques developed under Specific Aim 1 and 2, under experimental conditions which include the combined effects of photon attenuation, scatter radiation, noise, and partial volume effects. (4) Finally, the accuracy and precision of X-SPELT system will be determined for measurement of Tc-99m-MIBI uptake in a porcine model of myocardial perfusion to test the hypothesis that CT scans can be used to assess myocardial wall thickness to derive parameters to compensate the radionuclide data for partial volume effects, and to correct the correlated images for errors contributed by scattered radiation. These studies will evaluate the performance of the emission-transmission imaging for quantative radionuclide studies using Monte Carlo computer simulation, phantom studies, and experimental measurements in animals, with the intermediate goal of improving radionuclide assessments of myocardial perfusion, and with the long-term goal of applying these techniques to improve assessments of myocardial perfusion and tumor dosimetry in human patients obtained with single-photon radionclides.